The long-term goals of this proposed research are to use the well-defined H-Y antigenic system to: (1) study the regulation of the immune response against H-Y; (2) study the genetic regulation of the expression of H-Y antigen; and (3) further advance the field of immunogenetics of spermatozoa. The in vitro serological detection of the H-Y antigen on the surface of mouse spermatozoa and male epidermal cells, with the cytotoxic test, permitted the further analysis of the H-Y system as to huroral and cellular immune factors involved in H-Y incompatibility. Our specific aims are to gain insight into such questions as: (1) What role do suppressor cells or factors play in the (a) long-term survival of male skin grafts on females of certain strains of mice which nevertheless produce cytotoxic antibody, and (b) in the specific unresponsiveness to male skin rejection by multiparous females; and (2) whether or not the antigenic representation on the sperm surface is coded by the haploid genome of the sperm or the diploid complement of its precursor cells. In a broader context, in as much as H-Y incompatibility is now seen to be a system in which graft survival occurs despite an immune response (antibody production), it provides a parallel with the growth of antigenic tumors in hosts that produce antibody and therefore has relevance to cancer as well as to transplantation biology.